Abnormalities of insulin action are central to the pathogenesis of a variety of abnormal physiologic states. Consequently, knowledge of the cellular mechanisms of insulin's effects on glucose metabolism will lead to better understanding of the mechanisms of a variety of diseases. The overall goal of this research proposal is to investigate various aspects of the interaction between insulin and the glucose transport system. Insulin activates the glucose transport system by increasing the number of available glucose transport units, therefore increasing the Vmax of transport. The effect is not immediate and occurs with an initial temperature dependent lag time. Further characterization of the temporal relationship between the formation on insulin receptor complexes and the onset of insulin's effect on glucose transport will be performed. This will include studies of the effect of chemical perturbations of isolated cells on the time lag (coupling phase) of insulin action. Additionally the relationship between dissociation of insulin receptor complexes and termination of insulin activation of glucose transport will be assessed. Furthermore, the possible role of changes in cellular calcium metabolism as a intermediate event in insulin's activation of glucose transport will be investigated. Finally, the role of insulin in the longterm regulation of the capacity of the glucose transport system will be further explored. These studies will lead to better understanding of the cellular events underlying insulin's ability to activate glucose transport, and should sharpen our understanding of the mechanisms of disease states in which insulin action is abnormal.